EA010431B1 - Palladium-based coordination compound and method for preparing thereof - Google Patents

Abstract

Coordination compound having a formula (CHNO)[PdCl] is constructed from anions of tetrachlorpalladite [PdCl]and paired cation [CHNHCH(CH)CH(CH)OH], having general structureAcid-free method of obtaining the claimed compound provides that dry powder of palladium chloride is added into aqueous solution of 2-methylamino-1-phenyl-1-hydrochloric propanol interaction of which results in forming anions [PdCl]and the compound each of said with two simultaneously forming cations [CHNHCH(CH)CH(CH)OH]after which the reaction mixture is evaporated and the settled sediment is dried as a final product.The compound exhibits higher radioprotective activity and lesser toxicity, provides quicker achievement of radioprotective effect with possible repeated administration thereof, a method for obtaining thereof provides the purity of the final product and its stability.

Description

The claimed group of inventions relates to the chemistry of coordination compounds / 13, 14 / and medicine, and in particular to a method for producing a palladium-containing compound that is able to reduce the severity of the manifestation of radiation damage to the body during prophylactic administration and to have a therapeutic effect if radiation exposure has occurred (including radiotherapeutic procedures).

The development of the modern nuclear industry and the use of ionizing radiation sources in various fields of industrial activity, including radiation therapy, increase the likelihood of a person getting a radiation load when irreversible processes begin to occur in the body. To protect against the adverse effects of ionizing radiation, a set of measures has been developed at present, including medical methods for their prevention and treatment.

All drugs with radioprotective properties are divided into several groups.

1. Sulfur-containing radioprotectors, where the most important are aminoalkylthiols, aminoalkylthiosulfates, aminoalkylthiophosphates and derivatives of isothiuronium. A characteristic feature of the preparations of this group is a directly proportional dependence of the severity of the anti-radiation properties in terms of the dose reduction factor (FOOD) versus the administered dose / 1 /. A known drug in this group is cystamine dihydrochloride (dihydrochloride bis- (b-aminoethyl) disulfide). FOOD cystamine in humans at doses of 0.4, 0.6, 0.8, 1.2 is 1.0, 1.1, 1.2, 1.3, respectively.

2. Vasoactive pharmacological preparations with radioprotective activity. The most important of them are biogenic amines from the range of indolyl- / 3 /, aryl-, imidazolylalkylamines, which can cause local circulatory hypoxia in radiosensitive tissues. Prostaglandins and their synthetic derivatives also belong to this group. Quinoline derivatives with serotonergic activity act according to the same mechanism. The most developed drugs in this group are mexamine / 5 / and indralin / 3, 4 /. FOOD 1.3 and 1.4, respectively.

3. Hormonal preparations of the steroid structure and their non-steroidal analogues, accelerating the post-radiation recovery of myelopoiesis, which includes estrogens with their synthetic non-steroidal analogues - chlorotrianisene / 7 / and diethylstilbestrol / 8 /. Indometophene (1,1-di (4-methoxyphenyl) -2- (indolyl-3) butene-1) / 9 /, which exhibits a longer (within 2 weeks) radioprotective effect compared to estrogens, belongs to this series of anti-radiation drugs while maintaining relatively pronounced anti-radiation effectiveness (FUD = 1.2-1.3).

4. Long-acting anti-radiation drugs that realize their effect by changing the functional state of the body systems involved in myelopoiesis, which have a different natural origin and chemical structure. These are, first of all, polysaccharides and lipopolysaccharides, mainly of a bacterial nature / 10 /. Recently, granulocyte-macrophage factor (GM-CSF) and interleukin-3, acting at the level of multicommit stem cells, granulocyte (G-CSF) and macrophage (M-CSF) colony-stimulating factors, which realize their effect on commited CCMs, have gained the greatest popularity. Chitosan has found practical application.

5. Pharmacologically active compounds with pro-hypoxic properties, including p-aminopropiophenone and its derivatives, tetrazoles, cyanides, nitrites, drugs that reduce the level of wakefulness / 6 /.

6. Medicines that increase the nonspecific resistance of the body, a characteristic feature of which is good tolerance, as well as the possibility of re-using them as separate courses, the multivalency of the action, accompanied by favorable changes in the body, characterized by a general increase in its non-specific resistance not only to radiation, but and to factors of an infectious, stressful and hypoxic nature. These are natural stimulants for the synthesis of protein and nucleic acids (nucleotides, riboxin, orotic acid), natural antioxidants (vitamins C, E, A, carotene preparations, trace elements, etc.), amino acids and amino-vitamin preparations (aminotetravite, amevis, glutamevit etc.), natural adaptogens (preparations of ginseng, eleutherococcus, propolis, etc.), food additives (MIGI-K mussel hydrolyzate, KSP - milk hydrolyzate, etc.) / 11 /.

7. Means of early therapy for ARS, a feature of the anti-radiation effect of which is that they can be used both before irradiation and after. This group of drugs includes BCG vaccines, typhoparathyphoid, influenza, and other polysaccharides (prodigiosan / 10 / - a substance isolated from non-pathogenic bacillus Bact.prodigiosum, translam / 11 / - polysaccharide, 1 ^ 3, 1 ^ 6, З-Э -glucan obtained by enzymatic synthesis from laminaran - a polysaccharide of Far Eastern brown algae Laminaria cichorioides, betaleukin / 5 / - dosage form of recombinant human interleukin-1Z). The practical application was found by the drug deoxinate (sodium salt of DNA from sturgeon milk) / 5 /. The drug has a clear anti-radiation effect with a single injection or in the first 24 hours from exposure (FUD = 1.2-1.3).

The disadvantages of these drugs are:

the first group of drugs - poor tolerance of the doses necessary for the treatment and prevention of radiation injuries;

- 1 010431 of the second group - the possibility of only a single administration, due to the peculiarities of the pharmacological action (vasospasm);

the third group - the anti-radiation properties begin to manifest only 2 days after the start of administration, reach their maximum after 5-7 days;

the fourth group - positive therapeutic results are manifested only if applied in the early stages after irradiation, during the first 24 hours, narrow species specificity and high cost;

the fifth and sixth groups - the absence of specific tropism of these compounds with respect to radiosensitive tissues and, as a result, low radiation resistance, and in the sixth group, the slow achievement of radioresistance of the organism;

seventh group - the need for their immediate administration, low efficiency when administered after more than 24 hours

8. Currently, a new class of palladium-containing compounds with protonated aromatic amines of the general formula [NH ₂ R ₁ R ₂ ] ₂ [PdCl ₄ ] having a radioprotective effect / 12 / is described in the literature.

Compounds of this series were prepared by reacting stoichiometric amounts of 1- (4 nitrophenyl) -2-methylaminoethanol, 1- (4-nitrophenyl) -2-aminopropane-1,3-diol, 2- (3-hydroxyphenyl) -2ethylaminoethanol, 2-phenyl- 1-1-methylaminopropanol-2-ol with a solution of palladium dichloride in hydrochloric acid at 30-80 ° C, followed by isolation of the target product (acid method).

This production method makes it possible to contaminate the final product with traces of hydrochloric acid. An adverse factor in this case will be an increase in the acidity of the solutions of the dosage form.

Prolonged evaporation of solutions in order to remove residual hydrochloric acid causes a partial change in the structure of the final product, fixed by infrared spectroscopy, which leads to a decrease in radioprotective activity.

The yield of the finished product obtained by the acid method is 80-85%.

The radioprotective activity of the class of compounds described in [12] is characterized by FOOD - 1.1-1.2, toxicity - LD ₅₀ ³⁰ to 100 mg / kg (on mice CBA x C ₅₇ Bl / F ₁ ).

The technical task of the group of inventions related by a single inventive concept is to create an effective coordination radioprotective compound, as well as an effective and convenient way to obtain such compounds.

The technical result of this group of inventions is the creation of a compound with higher radioprotective activity and lower toxicity, providing a fairly rapid achievement of radioprotective effect and with the possibility of repeated administration, as well as developing a method for its preparation, ensuring the purity of the final product and its stability.

The essence of the invention in terms of substance is that the coordination compound with the formula (Ci ₀ H ₁₆ NO) ₂ [PdCl ₄ ] is constructed from anions of tetrachloropalladite [PdCl ₄ ] ^2- and paired cations

The essence of the invention in terms of the method consists in the fact that the acid-free method for producing the claimed compound provides that dry powder of palladium chloride is added to an aqueous solution of 2-methylamino-1-phenyl-1-propanol hydrochloride, the interaction of which leads to the formation of anions [PdCl ₄ ] ^2- and the combination of each of the latter with two simultaneously formed cations [CH3NH2CH (CH3) CH (C6H5) OH] ⁺ , after which the reaction mixture is evaporated and the precipitate formed is dried as the target product.

Preferably, 2 g (11.28 mmol) of palladium chloride are added to a solution of 2-methylamino-1-phenyl-1-propanol hydrochloride for every 4.55 g (22.56 mmol) of the latter and 14 ml of water, the reaction mixture is filtered and the filtrate evaporated at a temperature of 80 ± 2 ° C to a small volume, cooled, and the precipitated precipitate as a target product is dried at 80-90 ° C.

- 2 010431

The solution of this problem was carried out in the synthesis of the compound (CH ₃ NH ₂ R) 2 [PdCl4], where R = -CH (CH ₃ ) CH (C ₆ H ₅ ) OH obtained by the acid-free method by the interaction of an aqueous solution of 2-methylamino-hydrochloric acid 1-phenyl-1-propanol (L-HCl) with a fine powder of palladium dichloride (PdCl ₂ ) _n , followed by isolation of the target product (radiofence).

In the particular case of the implementation of this synthesis, 2 g (11.28 mmol) of palladium chloride are added to a solution of 4.55 g (22.56 mmol) of LHCl in 14 ml of water. The reaction solution is filtered and evaporated at 80 ± 2 ° C until a film of the synthesized substance appears on the surface of the solution. After cooling the solution, the precipitated crystalline substance is separated from the mother liquor and dried at 80-90 ° C. The yield of dry product is 96.5% (calculated on the introduced palladium).

For the composition of C ₂₀ H ₃₂ O ₂ N ₂ PdCl ₄ :

found (%): Pd - 18.33; Cl - 24.41; N - 4.80;

calculated (%): Pd - 18.34; Cl - 24.43; N - 4.83.

The structure of the coordination compound, named radiofence, was established by x-ray diffraction analysis. The crystals (C ₁₀ H ₁₆ NO) ₂ [PdCl ₄ ] are rhombic, a = 5.925 (1), b = 14.242 (4), c = 30.173 (11), z = 4, space group C222 ₁ .

The unit cell parameters and the intensity of 1357 reflections with I> 20 (I) were measured using a Syntex-P2 ₁ 4-circle automatic diffractometer (MoK _a - radiation, graphite monochromator, θ / 2θ scan 2θ _max = 50 °).

The structure was solved by the heavy atom method, and the least-squares method was refined in the full-matrix isotropic approximation. At this stage of refinement, a correction was introduced for the absorption of x-rays by the crystal according to the DIFABS method [1] (μ (ΚοΚ _α ) = 23.02 cm ^-1 ). Further refinement of the structure was carried out by the least squares method in the anisotron approximation for Pd, Cl, O, and N atoms and isotropic for carbon atoms. The coordinates of the H atoms at C and N are geometrically calculated, the position of the hydrogen of the OH group is localized in the difference synthesis of electron density. The final refinement of the least-squares method in the full-matrix anisotropic (for Pd, Cl, O, N) approximation and in the isotropic one for C atoms, taking into account the contribution of all H atoms with fixed positional and temperature parameters (Viso = 4.5 A ² ), was brought to R = 0, 0532, Rw = 0.0678 over 1034 reflections with F ² > 30 F ² . The atomic coordinates are given in table. one.

The crystal is built from anions | PdC? L ₄ | ^2- located on the 2 axis, and [CH ₃ NH ₂ CH (CH ₃ ) CH (C ₆ H ₅ ) OH] + cations, occupying a common position in the crystal. The structure of the complex and the geometric parameters of both structural units of the crystal are shown in FIG. 1 and 2. The bond lengths and bond angles are given in table. 2.

In the complex, the Pd atom has the usual plane-square coordination with the lengths of the Pd-Cl bonds (2,279 (3), 2,284 (4), and 2,301 (1)). In other structures containing the [PdCl ₄ ] ^2- anion, the Pd-Cl bond length varies within 2.29–2.32 A [2–9], slightly exceeding two of our values.

In FIG. Figure 3 shows the Newman projections along the NC (8) and C (8) -C (7) bonds of the cation and the torsion angles in the non-aromatic fragment of the cation are given. The methyl group at the N and C atoms (8) are in relative communication goshkonformatsii NC (8), the N atom and the hydroxyl group (OH) ^- are goshkonformatsii about the C (7) -C (8), and the N atom and phenyl group ^ 1) ^ (6) - trans conformations with respect to the same bond. This conformation of the cation is favorable for the formation of a complex system of hydrogen bonds uniting cations and anions. The cation has three active protons, each of which participates in hydrogen bonds with coordinated chlorine atoms of anions. The hydrogen bonding system in the crystal is shown schematically in FIG. 1. Fragments of NH ₂ pairs of cations perform a bridging function, combining [PdCl ₄ ] ^2- into infinite chains developing along the axis 2 of the crystal. Moreover, the OH groups of each pair are oriented to symmetrically bonded Cl atoms (Cl (3) and Cl (3 ')) of the same anion, forming hydrogen bonds with these atoms.

The investigated structure is characterized by the following geometric parameters of hydrogen bonds. The distance Cl (3) -H (0) is 2.31 for the sum of the van der Waals radii of 3.0 A, the angle Cl (3) -H-O is 155 °, and the angle OClPd is 109 °. All the parameters found correspond to a fairly strong hydrogen bond. Two symmetrically independent hydrogen bonds of the N-H-Cl type have noticeably different geometries. The distance O (1) -H (2) 2.19 A is shorter than the distance O (2) -H (1) 240 A, the angle Cl (1) -H (2) -N is 154 °, while the angle Cl (2) -H (1) -N - 136 °. These data indicate that Cl (1) H (2) -N type hydrogen bonds are stronger than Cl (2) -H (1) -N type hydrogen bonds. The latter allows us to suggest that upon dissolution of the compound, these last hydrogen bonds should be destroyed first of all, especially since they group structural units into infinite chains, i.e., the action of the entropy factor should be manifested in the destruction of ordered intermolecular formations. As for the other two intramolecular hydrogen bonds, under physiological saline conditions, they may well remain, moreover, the electrostatic interaction contributes to the close arrangement of the anion and cations. The above reasoning finds indirect confirmation in the features of the chemical behavior of the complex in solution. It was established that there is a substitution for water with the formation of the corresponding aquacomplex of only one Cl ligand, which suggests a screening from similar substitution of the three remaining chlorine atoms, that is, the existence of cations and anions in solution in the form of an ionic triad.

- 3 010431

In FIG. 1 shows the structure of the complex (dashed lines (hydrogen bonds) on the left and right indicate that a crystal is formed due to them), in FIG. 2 - parameters of structural units of the complex, in FIG. 3, the Newman projection along the bonds N-C (8) and C (8) -C (7) of the cation, in FIG. 4 is a graph of the effect of radiofence on the dynamics of early post-radiation recovery of CFUs in mice, where the abscissa shows the time between irradiation fractions in hours, and the ordinate shows the logarithm of the average number of endocolonies per spleen.

Table 1 tu ______________________ ________ 1L4 ______ τνκ, ιηΥ

Atom X Y Z Pd 0 14236 (7) 25,000 C1 (1) 0 3027 (3) 2500 Cl (2) 0 -177 (2) 2500 Cl (3) 721 (5) 1430 (2) 3249 (1) ABOUT 3844 (14) 3232 (5) 3503 (2) N 8058 (17) 4132 (6) 3314 (3) C (1) 5567 (17) 2261 (6) 4089 (3) C (2) 7259 (20) 1661 (7) 4223 (4) C (3) 7005 (22) 1135 (7) 4606 (4) C (4) 4975 (24) 1225 (7) 4861 (4) C (5) 3334 (24) 1820 (8) 4723 (4) C (6) 3609 (23) 2348 (8) 4348 (4) C (7) 5960 (21) 2847 (7) 3663 (3) C (8) 7485 (18) 3678 (7) 3754 (3) C (9) 9952 (27) 4809 (7) 3311 (4) C (10) 6531 (25) 4416 (9) 4074 (4)

table 2

The bond lengths (d, A) and bond angles (ω, degrees)

Radifens is a light brown powder, m.m. - 580.74 g / mol, soluble in water (8 g in 100 ml of water) and physiological saline (6 g in 100 ml of 0.9% NaCl), as well as in alcohol and acetone. Radifense is stable in air, not hygroscopic, stable in light, storage at 2030 ° C for 2 years did not reveal any changes in the product. Decomposition begins (according to thermogravimetric analysis) at 165 ° C (heating rate of the sample 2.5 ° / min).

Compound toxicity: LD ₅₀ ³⁰ = 150 mg / kg (CBAxC ₅₇ Bl / F ₁ mouse).

The radioprotective effect of radiofence is shown by the example of its influence on the value of FUD and the processes of post-radiation restoration of radiosensitive stem cells.

To establish the effect of radiofence on FUD, studies were conducted with irradiation of white inferior mice on an Agat-R apparatus in a static mode with a total radiation dose in various modes of 6 Gy. Prior to irradiation, animals (20 animals in each group) were administered: control group — saline, experimental groups — radiofence and prototype / 12 /. As a result of the studies, it was found that the prototype FOOD is 1.2, and the radiofence is up to 1.5.

The pharmacological effect of radiofence on the ability of cells to repair after irradiation in an in vivo system was studied using the fractional irradiation method and the application of protracted irradiation. Both of these methods are the most common and informative for the detection of post-radiation restoration of sublethal cell damage. As a test system, an assessment was made of the effect of radiofence on the defeat of radiosensitive hematopoietic stem cells, and in particular the method of endogenous colony formation, based on the ability of colony forming units (CFU) survivors to form clones in the spleen.

A method for studying the effect of radiofence on the dynamics of post-radiation restoration of hematopoietic colony forming units under conditions of fractionation of the radiation dose was as follows. The two radiation fractions are separated by relatively small time intervals, which exclude the possibility of the influence of cell proliferation factor during this period on the total effect of radiation. In a certain time interval (from 2 to 10 hours), a gradual increase in the yield of endocolonies with a maximum increase in post-radiation cell survival is detected in the case when the interval between the first and second fractions is about 10 hours, i.e. if the radiofence has the ability to positively influence the post-radiation restoration of cells, the effect will be manifested in a modification of the kinetics of CFU recovery (earlier peak, more pronounced increase in the number of CFU in the spleen compared to only irradiated animals without radiofence).

The experiments were performed on CBAxC ₅₇ Bl mice (males, body weight 22-24 g). Each group contained 10 animals. The dose of 7 Gy was divided into two fractions: 4 Gy + 3 Gy. The second fraction of gamma irradiation was modeled at different times after the first (after 2, 4, 6, 8, and 10 hours). The animals of the experimental groups immediately after the first irradiation in a dose of 4 Gy were injected once intravenously with radiofrequency at the rate of 17 mg / kg in a volume of 0.2 ml of physiological solution of sodium chloride. 8 days after irradiation, the animals were sacrificed by decapitation and the number of endocolonies in the spleen was counted. In control groups, animals were injected with 0.2 ml of physiological saline.

As can be seen from the results presented in FIG. 4, the introduction of radiofence contributed to the earlier achievement of the maximum values of the number of CFUs (when the interval between fractions is 8 hours). The number of CFU in the experimental groups statistically significantly exceeds the control values (only irradiation without drug administration), when the time interval between fractions is 8 and 10 hours

Thus, the experimental results indicate a positive modifying effect of radiofence on the repair of cellular damage after irradiation.

A study of the effect of radiofence on endogenous colony formation under protagulated irradiation makes it possible to identify elements of the radioprotective mechanism of radiofence, which reduces to establishing its modifying effect in the in vivo system on post-radiation cellular recovery during prolonged irradiation (radiation dose rate effect).

The effect of radiofence on the CFUc yield in CBAxC57Bl hybrid mice exposed to radiation at a LUCH gamma-ray unit in a total absorbed dose of 6 Gy was studied. Each group consisted of 10 animals. Completed 4 series of experiments. In two series of experiments during irradiation with a power of 2 and 0.5 rad./min and, accordingly, an irradiation time of 5 and 20 hours, radiofence was administered once intravenously 15 mg / kg immediately before the start of irradiation. The third group of animals was irradiated in a total absorbing dose of 6 Gy with a dose rate of 0.5 rad./min. The irradiation time was 21 hours. However, radiofence was administered twice at a dose of 15 mg / kg: immediately before irradiation and 10 hours 30 minutes after the start of irradiation. 8 days after completion of irradiation, the number of endocolonies in the spleen was counted. The results are presented in table. 3.

Table 3

The effect of radiofence on the number of endogenous CFUs

Unit dose rate of γ-radiation rad / min Time exposure The number of endogenous CFUs (M + GP) Only irradiation Irradiation + Radiation 1x introduction 2x introduction 2 5 hour 7.7 ± 0.75 12.7 ± 1.13 - 0.5 20 hour b, 6 ± 1.2b 6.6 ± 0.78 - 0.5 21 hours 09 mins 7.3 ± 0.52 - 9.4 ± 0.83

As can be seen from the table. 3, in the group of irradiated mice only, the change in dose rate did not cause statistically significant differences in the number of splenic endocolonies. A single administration of radiofence significantly increased the yield of endocolonies upon irradiation with a dose rate of 2 rad./min. This fact indicates the involvement of radiofence in the repair of sublethal cellular damage.

- 5 010431

However, with a further decrease in the dose rate to 0.5 rad./min and an increase in the irradiation time, the radiofence showed no modifying effect. It is likely that in this formulation of the experiment (when irradiation lasted for 20 hours) a single injection of the drug was insufficient to realize its radioprotective effect. The secondary administration of radiofence in the middle of the irradiation period, after 10 h 30 min, provided a statistically significant yield of splenic endocolonies, i.e. the second introduction of radiofence turned out to be sufficient to realize the radioprotective effect of radiofence.

A generalization of the experimental data obtained in experiments in vivo under conditions of fractionated exposure and irradiation with different dose rates indicates that radiofence has a radioprotective effect and one of the possible mechanisms of radioprotective action of radiofence is its participation in the repair of sublethal cellular injuries.

Conclusion

Thus, the coordination compound (C ₁₀ H ₁₆ NO) ₂ [PdCl4] is obtained, which has an increased radioprotective effect, which allows to expand the arsenal of means of protection against radiation damage.

An acid-free method has been developed to obtain the coordination compound of palladium, ensuring its high yield (up to 97%) and purity (content of the main product up to 99.5%).

Information sources

1. Vasin 1Ch.V., Saksonov P.P., Shashkov B.C., Antipov V.V. Antiradiation activity of aminothiols (cystamine), depending on the dose of the drug and the duration of its use under various conditions of gamma radiation // Radiobiol. 1970.V. 10, issue 3. S.380-384

2. Torp D., Bank P., Wendt T.G. et al. Daily amifostine given concomitantly to chemoradiation in head and neck cancer. A pilot study // Strahlenther. Oncol. 1999. Vol. 175, No. 9. P.444-449.

3. Zherebchenko P.G. Antiradiation drugs of indolylalkylamines. M .: Atomizdat, 1971, 200 p.

4. Vasin 1Ch.V., Antipov VV, Chernov G.A. et al. The role of the vasoconstrictor effect in the implementation of the antiradiation properties of indraline in experiments on dogs // Radiats. biol. Radioecol. 1997. Vol. 37, No. 1, C46-55.

5. Ilyin L.A. The theoretical basis of radiation medicine. M .: Publishing house AT, 2004. T1. 992 p.

6. Ilyin L.A. The basics of protecting the body from exposure to radioactive substances. M .: Atomizdat, 1977.256 s.

7. Flemming K., Langendorff M. Untersuchungen uber einen biologischen strahlenschutz. Mitt. 66. Das pro-ostrogen chlortrianisen (Tace) als Strahlenschutzsubstancz // Strahlenther. 1965. Bd. 128, No. 1. S.109-118.

8. Suslikov VN On the protective effect of diethylstilbestrol // Radiobiol. 1963. V. 3, No. 6. S. 880-890.

9. Vorotnikova T.V. Investigation of the mechanism of radioprotective action of indometophene and diethylstilbestrol on the blood system: Abstract. dis. Cand. honey. sciences. M., 1995.28 s.

10. Andrushchenko V.I., Ivanov A.A., Maltsev V.P. Antiradiation effect of substances of microbial origin // Radiats.biol. Radioecol. 1996. Vol. 36, No. 2, C195-208.

11. Vasin 1CH.V. Means of prevention and treatment of radiation injuries. M.: Ministry of Defense of the Russian Federation, 2000.264 s.

12. RU No. 2022968, 1994 (prototype).

13. E.E. Criss, I.I. Volchenskova, A.S. Grigoryeva, K.B. and others. Coordination compounds of metals in medicine. - Kiev .: Publishing house of the Naukov Dumka, 1986. 216 p.

14. K. Nakamoto. Infrared spectrum of inorganic and coordination compounds. - Moscow .: Mir Publishing House, 1966. 327s.

Claims (3)

CLAIM 1. The coordination compound of palladium with the formula (C ₁₀ H ₁₆ NO) ₂ [PdCl ₄ ], formed from the anions of tetrachloropalladite [PdCl ₄ ] ^{2 -} and paired cations [CH ₃ NH ₂ CH (CH ₃ ) CH (C ₆ H ₅ ) OH] + obtained by reacting an aqueous solution of 2-methylamino-1-phenyl-1-propanol hydrochloride with a dry powder of palladium chloride, with the general structure - 6 010431 2. The acid-free method for producing the compound according to claim 1, wherein dry powder of palladium chloride is added to an aqueous solution of 2-methylamino-1-phenyl-1-propanol hydrochloride, after which the reaction mixture is evaporated and the precipitate formed is dried to obtain the desired product. 3. The method according to claim 2, characterized in that 2 g are added to a solution of 2-methylamino-1-phenyl-1-propanol hydrochloride for every 4.55 g (22.56 mmol) of the latter and 14 ml of water (11, 28 mmol) of palladium chloride, the reaction mixture is filtered and the filtrate is evaporated at a temperature of 80 ± 2 ° C to a small volume, cooled, and the precipitated precipitate as a target product is dried at 80-90 ° C.